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Whole blood co-expression modules associate with metabolic traits and type 2 diabetes: an IMI-DIRECT study

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Harvard

Gudmundsdottir, V, Pedersen, HK, Mazzoni, G, Allin, KH, Artati, A, Beulens, JW, Banasik, K, Brorsson, C, Cederberg, H, Chabanova, E, De Masi, F, Elders, PJ, Forgie, I, Giordano, GN, Grallert, H, Gupta, R, Haid, M, Hansen, T, Hansen, TH, Hattersley, AT, Heggie, A, Hong, M-G, Jones, AG, Koivula, R, Kokkola, T, Laakso, M, Løngreen, P, Mahajan, A, Mari, A, McDonald, TJ, McEvoy, D, Musholt, PB, Pavo, I, Prehn, C, Ruetten, H, Ridderstråle, M, Rutters, F, Sharma, S, Slieker, RC, Syed, A, Tajes, JF, Thomas, CE, Thomsen, HS, Vangipurapu, J, Vestergaard, H, Viñuela, A, Wesolowska-Andersen, A, Walker, M, Adamski, J, Schwenk, JM, McCarthy, MI, Pearson, E, Dermitzakis, E, Franks, PW, Pedersen, O & Brunak, S 2020, 'Whole blood co-expression modules associate with metabolic traits and type 2 diabetes: an IMI-DIRECT study', Genome Medicine, vol. 12, no. 1, pp. 109. https://doi.org/10.1186/s13073-020-00806-6

APA

Gudmundsdottir, V., Pedersen, H. K., Mazzoni, G., Allin, K. H., Artati, A., Beulens, J. W., Banasik, K., Brorsson, C., Cederberg, H., Chabanova, E., De Masi, F., Elders, P. J., Forgie, I., Giordano, G. N., Grallert, H., Gupta, R., Haid, M., Hansen, T., Hansen, T. H., ... Brunak, S. (2020). Whole blood co-expression modules associate with metabolic traits and type 2 diabetes: an IMI-DIRECT study. Genome Medicine, 12(1), 109. https://doi.org/10.1186/s13073-020-00806-6

CBE

Gudmundsdottir V, Pedersen HK, Mazzoni G, Allin KH, Artati A, Beulens JW, Banasik K, Brorsson C, Cederberg H, Chabanova E, De Masi F, Elders PJ, Forgie I, Giordano GN, Grallert H, Gupta R, Haid M, Hansen T, Hansen TH, Hattersley AT, Heggie A, Hong M-G, Jones AG, Koivula R, Kokkola T, Laakso M, Løngreen P, Mahajan A, Mari A, McDonald TJ, McEvoy D, Musholt PB, Pavo I, Prehn C, Ruetten H, Ridderstråle M, Rutters F, Sharma S, Slieker RC, Syed A, Tajes JF, Thomas CE, Thomsen HS, Vangipurapu J, Vestergaard H, Viñuela A, Wesolowska-Andersen A, Walker M, Adamski J, Schwenk JM, McCarthy MI, Pearson E, Dermitzakis E, Franks PW, Pedersen O, Brunak S. 2020. Whole blood co-expression modules associate with metabolic traits and type 2 diabetes: an IMI-DIRECT study. Genome Medicine. 12(1):109. https://doi.org/10.1186/s13073-020-00806-6

MLA

Vancouver

Author

Gudmundsdottir, Valborg ; Pedersen, Helle Krogh ; Mazzoni, Gianluca ; Allin, Kristine H ; Artati, Anna ; Beulens, Joline W ; Banasik, Karina ; Brorsson, Caroline ; Cederberg, Henna ; Chabanova, Elizaveta ; De Masi, Federico ; Elders, Petra J ; Forgie, Ian ; Giordano, Giuseppe N ; Grallert, Harald ; Gupta, Ramneek ; Haid, Mark ; Hansen, Torben ; Hansen, Tue H ; Hattersley, Andrew T ; Heggie, Alison ; Hong, Mun-Gwan ; Jones, Angus G ; Koivula, Robert ; Kokkola, Tarja ; Laakso, Markku ; Løngreen, Peter ; Mahajan, Anubha ; Mari, Andrea ; McDonald, Timothy J ; McEvoy, Donna ; Musholt, Petra B ; Pavo, Imre ; Prehn, Cornelia ; Ruetten, Hartmut ; Ridderstråle, Martin ; Rutters, Femke ; Sharma, Sapna ; Slieker, Roderick C ; Syed, Ali ; Tajes, Juan Fernandez ; Thomas, Cecilia Engel ; Thomsen, Henrik S ; Vangipurapu, Jagadish ; Vestergaard, Henrik ; Viñuela, Ana ; Wesolowska-Andersen, Agata ; Walker, Mark ; Adamski, Jerzy ; Schwenk, Jochen M ; McCarthy, Mark I ; Pearson, Ewan ; Dermitzakis, Emmanouil ; Franks, Paul W ; Pedersen, Oluf ; Brunak, Søren. / Whole blood co-expression modules associate with metabolic traits and type 2 diabetes : an IMI-DIRECT study. In: Genome Medicine. 2020 ; Vol. 12, No. 1. pp. 109.

Bibtex

@article{45d8af7a9b3f471993960c0893d0560d,
title = "Whole blood co-expression modules associate with metabolic traits and type 2 diabetes: an IMI-DIRECT study",
abstract = "BACKGROUND: The rising prevalence of type 2 diabetes (T2D) poses a major global challenge. It remains unresolved to what extent transcriptomic signatures of metabolic dysregulation and T2D can be observed in easily accessible tissues such as blood. Additionally, large-scale human studies are required to further our understanding of the putative inflammatory component of insulin resistance and T2D. Here we used transcriptomics data from individuals with (n = 789) and without (n = 2127) T2D from the IMI-DIRECT cohorts to describe the co-expression structure of whole blood that mainly reflects processes and cell types of the immune system, and how it relates to metabolically relevant clinical traits and T2D.METHODS: Clusters of co-expressed genes were identified in the non-diabetic IMI-DIRECT cohort and evaluated with regard to stability, as well as preservation and rewiring in the cohort of individuals with T2D. We performed functional and immune cell signature enrichment analyses, and a genome-wide association study to describe the genetic regulation of the modules. Phenotypic and trans-omics associations of the transcriptomic modules were investigated across both IMI-DIRECT cohorts.RESULTS: We identified 55 whole blood co-expression modules, some of which clustered in larger super-modules. We identified a large number of associations between these transcriptomic modules and measures of insulin action and glucose tolerance. Some of the metabolically linked modules reflect neutrophil-lymphocyte ratio in blood while others are independent of white blood cell estimates, including a module of genes encoding neutrophil granule proteins with antibacterial properties for which the strongest associations with clinical traits and T2D status were observed. Through the integration of genetic and multi-omics data, we provide a holistic view of the regulation and molecular context of whole blood transcriptomic modules. We furthermore identified an overlap between genetic signals for T2D and co-expression modules involved in type II interferon signaling.CONCLUSIONS: Our results offer a large-scale map of whole blood transcriptomic modules in the context of metabolic disease and point to novel biological candidates for future studies related to T2D.",
author = "Valborg Gudmundsdottir and Pedersen, {Helle Krogh} and Gianluca Mazzoni and Allin, {Kristine H} and Anna Artati and Beulens, {Joline W} and Karina Banasik and Caroline Brorsson and Henna Cederberg and Elizaveta Chabanova and {De Masi}, Federico and Elders, {Petra J} and Ian Forgie and Giordano, {Giuseppe N} and Harald Grallert and Ramneek Gupta and Mark Haid and Torben Hansen and Hansen, {Tue H} and Hattersley, {Andrew T} and Alison Heggie and Mun-Gwan Hong and Jones, {Angus G} and Robert Koivula and Tarja Kokkola and Markku Laakso and Peter L{\o}ngreen and Anubha Mahajan and Andrea Mari and McDonald, {Timothy J} and Donna McEvoy and Musholt, {Petra B} and Imre Pavo and Cornelia Prehn and Hartmut Ruetten and Martin Ridderstr{\aa}le and Femke Rutters and Sapna Sharma and Slieker, {Roderick C} and Ali Syed and Tajes, {Juan Fernandez} and Thomas, {Cecilia Engel} and Thomsen, {Henrik S} and Jagadish Vangipurapu and Henrik Vestergaard and Ana Vi{\~n}uela and Agata Wesolowska-Andersen and Mark Walker and Jerzy Adamski and Schwenk, {Jochen M} and McCarthy, {Mark I} and Ewan Pearson and Emmanouil Dermitzakis and Franks, {Paul W} and Oluf Pedersen and S{\o}ren Brunak",
year = "2020",
month = dec,
day = "1",
doi = "10.1186/s13073-020-00806-6",
language = "English",
volume = "12",
pages = "109",
journal = "Genome Medicine",
issn = "1756-994X",
publisher = "BioMed Central Ltd",
number = "1",

}

RIS

TY - JOUR

T1 - Whole blood co-expression modules associate with metabolic traits and type 2 diabetes

T2 - an IMI-DIRECT study

AU - Gudmundsdottir, Valborg

AU - Pedersen, Helle Krogh

AU - Mazzoni, Gianluca

AU - Allin, Kristine H

AU - Artati, Anna

AU - Beulens, Joline W

AU - Banasik, Karina

AU - Brorsson, Caroline

AU - Cederberg, Henna

AU - Chabanova, Elizaveta

AU - De Masi, Federico

AU - Elders, Petra J

AU - Forgie, Ian

AU - Giordano, Giuseppe N

AU - Grallert, Harald

AU - Gupta, Ramneek

AU - Haid, Mark

AU - Hansen, Torben

AU - Hansen, Tue H

AU - Hattersley, Andrew T

AU - Heggie, Alison

AU - Hong, Mun-Gwan

AU - Jones, Angus G

AU - Koivula, Robert

AU - Kokkola, Tarja

AU - Laakso, Markku

AU - Løngreen, Peter

AU - Mahajan, Anubha

AU - Mari, Andrea

AU - McDonald, Timothy J

AU - McEvoy, Donna

AU - Musholt, Petra B

AU - Pavo, Imre

AU - Prehn, Cornelia

AU - Ruetten, Hartmut

AU - Ridderstråle, Martin

AU - Rutters, Femke

AU - Sharma, Sapna

AU - Slieker, Roderick C

AU - Syed, Ali

AU - Tajes, Juan Fernandez

AU - Thomas, Cecilia Engel

AU - Thomsen, Henrik S

AU - Vangipurapu, Jagadish

AU - Vestergaard, Henrik

AU - Viñuela, Ana

AU - Wesolowska-Andersen, Agata

AU - Walker, Mark

AU - Adamski, Jerzy

AU - Schwenk, Jochen M

AU - McCarthy, Mark I

AU - Pearson, Ewan

AU - Dermitzakis, Emmanouil

AU - Franks, Paul W

AU - Pedersen, Oluf

AU - Brunak, Søren

PY - 2020/12/1

Y1 - 2020/12/1

N2 - BACKGROUND: The rising prevalence of type 2 diabetes (T2D) poses a major global challenge. It remains unresolved to what extent transcriptomic signatures of metabolic dysregulation and T2D can be observed in easily accessible tissues such as blood. Additionally, large-scale human studies are required to further our understanding of the putative inflammatory component of insulin resistance and T2D. Here we used transcriptomics data from individuals with (n = 789) and without (n = 2127) T2D from the IMI-DIRECT cohorts to describe the co-expression structure of whole blood that mainly reflects processes and cell types of the immune system, and how it relates to metabolically relevant clinical traits and T2D.METHODS: Clusters of co-expressed genes were identified in the non-diabetic IMI-DIRECT cohort and evaluated with regard to stability, as well as preservation and rewiring in the cohort of individuals with T2D. We performed functional and immune cell signature enrichment analyses, and a genome-wide association study to describe the genetic regulation of the modules. Phenotypic and trans-omics associations of the transcriptomic modules were investigated across both IMI-DIRECT cohorts.RESULTS: We identified 55 whole blood co-expression modules, some of which clustered in larger super-modules. We identified a large number of associations between these transcriptomic modules and measures of insulin action and glucose tolerance. Some of the metabolically linked modules reflect neutrophil-lymphocyte ratio in blood while others are independent of white blood cell estimates, including a module of genes encoding neutrophil granule proteins with antibacterial properties for which the strongest associations with clinical traits and T2D status were observed. Through the integration of genetic and multi-omics data, we provide a holistic view of the regulation and molecular context of whole blood transcriptomic modules. We furthermore identified an overlap between genetic signals for T2D and co-expression modules involved in type II interferon signaling.CONCLUSIONS: Our results offer a large-scale map of whole blood transcriptomic modules in the context of metabolic disease and point to novel biological candidates for future studies related to T2D.

AB - BACKGROUND: The rising prevalence of type 2 diabetes (T2D) poses a major global challenge. It remains unresolved to what extent transcriptomic signatures of metabolic dysregulation and T2D can be observed in easily accessible tissues such as blood. Additionally, large-scale human studies are required to further our understanding of the putative inflammatory component of insulin resistance and T2D. Here we used transcriptomics data from individuals with (n = 789) and without (n = 2127) T2D from the IMI-DIRECT cohorts to describe the co-expression structure of whole blood that mainly reflects processes and cell types of the immune system, and how it relates to metabolically relevant clinical traits and T2D.METHODS: Clusters of co-expressed genes were identified in the non-diabetic IMI-DIRECT cohort and evaluated with regard to stability, as well as preservation and rewiring in the cohort of individuals with T2D. We performed functional and immune cell signature enrichment analyses, and a genome-wide association study to describe the genetic regulation of the modules. Phenotypic and trans-omics associations of the transcriptomic modules were investigated across both IMI-DIRECT cohorts.RESULTS: We identified 55 whole blood co-expression modules, some of which clustered in larger super-modules. We identified a large number of associations between these transcriptomic modules and measures of insulin action and glucose tolerance. Some of the metabolically linked modules reflect neutrophil-lymphocyte ratio in blood while others are independent of white blood cell estimates, including a module of genes encoding neutrophil granule proteins with antibacterial properties for which the strongest associations with clinical traits and T2D status were observed. Through the integration of genetic and multi-omics data, we provide a holistic view of the regulation and molecular context of whole blood transcriptomic modules. We furthermore identified an overlap between genetic signals for T2D and co-expression modules involved in type II interferon signaling.CONCLUSIONS: Our results offer a large-scale map of whole blood transcriptomic modules in the context of metabolic disease and point to novel biological candidates for future studies related to T2D.

U2 - 10.1186/s13073-020-00806-6

DO - 10.1186/s13073-020-00806-6

M3 - Journal article

C2 - 33261667

VL - 12

SP - 109

JO - Genome Medicine

JF - Genome Medicine

SN - 1756-994X

IS - 1

ER -

ID: 61505156